Body mass is a major determinant of bone mass. This effect is not adequately explained by either mechanical hypothesis (increased loading) or the higher estrogen status associated with increased fat, suggesting some other link between body mass and bone mass. Leptin, the newly discovered adiposite- derived satiety hormone, may constitute the sought- for link between fat mass and bone mass. Matkovic et al. (1997a and b) have shown that leptin may have an anabolic effect on periosteal bone formation. Furthermore, Liu et al. (1997) have shown that leptin given to ob/ob mice produces a dramatic increase in endocortical bone formation. At the present time, no other work has been done on leptin bone interactions. We propose to examine the inter-relationship between leptin and bone formation using the adult rat as a model. We will test the hypothesis that bone response to leptin 1) is anabolic and results in an increase in bone mass and strength, 2) is dose dependent, 3) occurs in both cancellous and cortical bone, 4) effects the periosteal and endosteal surfaces, and 5) is independent of estrogen status. Densitometric, biomechanical, and histomorphometric response will be assessed.